Abstract: The metabolism of cancer cells is different from that of their normal cell counterparts. Known as the Warburg effect (or aerobic glycolysis), this altered tumor cell metabolism is characterized by enhanced lactate production with reduced oxidative phosphorylation even in the presence of oxygen. Although this observation was first made over 75 years ago, how cancer cells establish this altered metabolism and whether it is important for tumorigenesis remains unknown. Our research aims to determine the molecular mechanisms by which tumor cells establish and maintain the Warburg effect in cancer, to definitively address whether the Warburg effect is necessary for tumor growth, and to identify novel cancer drug targets responsible for maintenance of the Warburg effect in vivo. This study will determine whether targeting cancer metabolism is a viable approach for cancer therapy and will better define the role of metabolism for tumor growth. Public Health Relevance: This proposed research will investigate causes of the altered metabolism found in cancer cells. It will also test whether targeting this altered metabolism is a viable strategy for cancer therapeutics.